Corcept Therapeutics, Inc.

Patent Trials and Appeals Board

Oct 15, 2020

2020005311 (P.T.A.B. Oct. 15, 2020)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
14/020,205 09/06/2013 Joseph K. Belanoff 85178-886534 (004520US) 1586
144579 7590 10/15/2020
KILPATRICK TOWNSEND & STOCKTON LLP/CORCEPT
Mailstop: IP Docketing - 22
1100 Peachtree Street
Suite 2800
Atlanta, GA 30309
EXAMINER
CRUZ, KATHRIEN ANN
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
10/15/2020 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
KTSDocketing2@kilpatrick.foundationip.com
ipefiling@kilpatricktownsend.com
jfox@corcept.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte JOSEPH K. BELANOFF
____________

Appeal 2020-005311
Application 14/020,205
Technology Center 1600
____________

BEFORE DONALD E. ADAMS, ULRIKE W. JENKS, and
TAWEN CHANG, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s
decision to reject claims 1, 15, 17–26, and 28–33 (see Appellant’s July 13,
2020 Reply Br. 2).2 We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the real party in interest as “Corcept
Therapeutics, Inc.” (Appellant’s February 3, 2020 Appeal Brief (Appeal Br.)
3).
2 Appellant’s Appeal Brief includes claim 27 in its listing of the claim status
(see Appeal Br. 5). We note, however, that Appellant’s Reply Brief
correctly excludes claim 27 from the status of the claims (see Reply Br. 2;
see also Appellant’s July 2, 2019 Response 5 (“Claim 27 has been
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STATEMENT OF THE CASE
Appellant’s disclosure “relates to the discovery that an agent capable
of antagonizing the binding of cortisol to a glucocorticoid receptor is useful
in methods for treating a patient diagnosed with Amyotrophic Lateral
Sclerosis (ALS).” (Spec. ¶ 2).
During prosecution Examiner required Appellant to elect, for
examination purposes, “one particular non-[steroidal] glucocorticoid
receptor specific antagonist (complete with chemical name and structure)”
(Examiner’s January 2, 2014 Office Action). In response, Appellant elected
the non-steroidal glucocorticoid receptor specific antagonist:
(R)-6-(4-tert-Butyl-benzenesulfonyl)-4a-ethoxymethyl-1-(4-
fluoro-phenyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-
cyclopenta[b]naphthalene, having the following structure:

.
(Appellant’s February 28, 2014 Response 2.)
Appellant’s claims 1, 15, and 25 are reproduced below:
1. A method for ameliorating the symptoms and/or
slowing the rate of disease progression in a patient diagnosed
with amyotrophic lateral sclerosis (ALS), the method
comprising: administering daily doses of a therapeutically
effective amount of a non-steroidal glucocorticoid receptor
specific antagonist (GRA) to a subject in need thereof, wherein
the glucocorticoid receptor antagonist is administered in a daily

canceled”); Examiner’s September 10, 2019 Office Action (Appellants
“response filed 7/2/2019 has been received and entered in the application”)).
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amount of between about 0.5 mg and about 40 mg per kg of
body weight per day, and wherein said GRA specifically
antagonizes type II glucocorticoid receptor functions but does
not significantly antagonize type I glucocorticoid receptor
(mineralocorticoid receptor) functions, with the proviso that the
subject not be otherwise in need of treatment with a
glucocorticoid receptor antagonist, whereby said symptoms are
ameliorated and/or the rate of disease progression is slowed in
said ALS patient.
(Appeal Br. 33.)
15. The method of claim 1, wherein the glucocorticoid receptor
antagonist is an azadecalin or a fused ring azadecalin
compound.
(Id.)
25. The method of claim 1, wherein the binding affinity of the
GRA for the type II glucocorticoid receptor is at least 100-fold
greater than the binding affinity of the GRA for the type I
glucocorticoid receptor (mineralocorticoid receptor).
(Id. at 34.)
Due to the species election discussed above, we review Appellant’s
claimed invention in the context of a non-steroidal glucocorticoid receptor
specific antagonist (GRA) that is (R)-6-(4-tert-Butyl-benzenesulfonyl)-4a-
ethoxymethyl-1-(4-fluoro-phenyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-
cyclopenta[b]naphthalene. See generally Ex parte Ohsaka, 2 USPQ2d 1460,
1461 (BPAI 1987).
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Claims 1, 15, 17–26, and 28–33 stand rejected under 35 U.S.C.
§ 103(a) as unpatentable over the combination of Clark,3 Carrὶ,4 and Sapse.5
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. Clark discloses that “GR modulators may . . . affect a wide variety of
disease states, such as . . . neurodegeneration (e.g. Alzheimer’s disease and
Parkinson’s disease)” (Clark ¶ 66; see Ans. 4).
FF 2. Clark “provides methods of treating a disorder or condition through
antagonizing a glucocorticoid receptor,” wherein “[t]he method includes
administering to a subject in need of such treatment, an effective amount of
[Clark’s disclosed] compound” (Clark ¶ 15).
FF 3. Clark discloses “a novel class of fused ring azadecalin compounds
and methods of using the compounds as glucocorticoid receptor [(GR)]
modulators” (Clark, Abstract; see Ans. 4; see also Appellant’s February 28,
2014 Response 2 (citing Clark ¶ 365) (Appellant recognizes that Clark
expressly discloses Appellant’s elected non-steroidal glucocorticoid receptor
specific antagonist (GRA), (R)-6-(4-tert-Butyl-benzenesulfonyl)-4a-
ethoxymethyl-1-(4-fluoro-phenyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-
cyclopenta[b]naphthalene)).

3 Clark et al., WO 2005/087769 A1, published Sept. 22, 2005.
4 Carrὶ et al., Neurodegeneration in amyotrophic lateral sclerosis: the role
of oxidative stress and altered homeostatsis of metals, 61 Brain Research
Bulletin 365–374 (2003).
5 Sapse et al., US 2005/0085464 A1, published Apr. 21, 2005.
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FF 4. Clark discloses “pharmaceutical formulations for oral administration
of GR modulator is in a daily amount of between about 0.5 to about 20 mg
per kilogram of body weight per day” (Clark ¶ 233; see Ans. 4).
FF 5. Examiner finds that although Clark discloses the use of a GR
modulator to treat neurodegenerative disorders, Clark does not expressly
disclose the treatment of “amyotrophic lateral sclerosis (ALS)” (Ans. 5).
FF 6. Carrὶ discloses that ALS “is one of the most common
neurodegenerative disorders” (Carrὶ, Abstract; see Ans. 5).
FF 7. Examiner relies on Sapse to disclose “that tracking and treating
increased levels of cortisol could be used to treat or prevent high cortisol
diseases such as . . . [ALS], where elevated cortisol is constantly found”
(Ans. 5 (citing Sapse ¶ 4) (emphasis omitted)).
ANALYSIS
Based on the combination of Clark, Carrὶ, and Sapse, Examiner
concludes that, at the time Appellant’s invention was made, it would have
been prima facie obvious to treat ALS, the most common neurodegenerative
disorder, by administering (R)-6-(4-tert-Butyl-benzenesulfonyl)-4a-
ethoxymethyl-1-(4-fluoro-phenyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-
cyclopenta[b]naphthalene at a dosage of 0.5 to about 20 mg per kilogram of
body weight per day (see generally Ans. 5–6; see also FF 1–6). See Iron
Grip Barbell Co. v. USA Sports, Inc., 392 F.3d 1317, 1322 (Fed. Cir. 2004)
(“[W]here there is a range disclosed in the prior art, and the claimed
invention falls within that range, there is a presumption of obviousness.”).
In sum, the combination of Clark, Carrὶ, and Sapse makes obvious the
treatment, i.e. amelioration and/or slowing the rate of disease progression, of
a neurodegenerative disorder, such as ALS, in a subject by administering
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Appellant’s elected non-steroidal glucocorticoid receptor specific antagonist
(GRA), to a patient in need of such treatment, in an amount that falls within
that required by Appellant’s claimed invention (see FF 1–6). Because the
GRA taught by the prior art relied upon by Examiner is the same GRA
elected by Appellant we find no error in Examiner’s finding that the prior art
GRA: (a) is a fused ring azadecalin compound; (b) will specifically
antagonize type II glucocorticoid receptor functions but will not significantly
antagonize type I glucocorticoid receptor (mineralcorticoid receptor)
functions; and (c) has a binding affinity for the type II glucocorticoid
receptor that is at least 100-fold greater than the binding affinity of the GRA
for the type I glucocorticoid receptor (mineralocorticoid receptor) (see, e.g.,
Ans. 8, and 25; see also FF 1–6).

Claim 1:
Clark expressly discloses the administration of an effective amount6
of a compound that antagonizes a glucocorticoid receptor, i.e. Appellant’s
elected GRA, to treat, inter alia, a neurodegeneration disorder (see FF 1–4
(emphasis added)). ALS “is one of the most common neurodegenerative
disorders” (FF 6). Therefore, we are not persuaded by Appellant’s
contention that the combination of Clark, Carrὶ, and Sapse “does not teach
the use of GR antagonists to affect neurodegeneration, and makes no
suggestion that GR antagonists might be used to treat ALS” (Appeal Br. 13
(citing Clark Decl.7 ¶¶ 7 and 9–11); see also Appeal Br. 18 (Appellant

6 For example, the daily oral administration of between about 0.5 to about 20
mg per kilogram of body weight per day (see FF 4).
7 Declaration of Robin D. Clark, Ph.D., signed Sept. 16, 2015.
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contends that “Examiner . . . presented no evidence that one class of drugs,
such as non-steroidal GRA’s, can be used to effectively treat different
neurodegenerative diseases” or that the references cited by Examiner
“contradict each other”); Reply Br. 14–15 (Appellant contends that “because
[Carrὶ ] suggests that metal-mediated oxidative stress was thought to be one
of the main mechanisms in the pathogenesis of ALS, and [Carrὶ] does not
provide any guidance on administering GRAs to treat a symptom of ALS”
“a person of ordinary skill in the art reading [Carrὶ] would not be motivated
to treat ALS with the claimed GRA, and would not have a reasonable
expectation of success”)).
For the foregoing reasons, we are not persuaded by Appellant’s
contention that “Clark discusses GR ‘modulators’ yet provides no suggestion
or guidance to select GR antagonists; thus, there is no teaching or suggestion
in the reference leading one of ordinary skill in the art to modify Clark in
order to provide the claimed treatment for ALS” (Appeal Br. 14 (emphasis
omitted); see id. at 21 (Appellant contends that “Clark does not provide any
guidance on what type of GR modulator would be suitable to treat a given
neurodegenerative disease, let alone that a GRA would be effective”)). For
the same reasons, we are not persuaded by Appellant’s contention that
“[n]one of the cited references provide a ‘detailed enabling methodology’
for treating ALS with the claimed GRA, and none of the cited references,
nor their combination, provide any evidence suggesting that it would be
successful, therefore claim 1 is not obvious in view of the cited references”
(Appeal Br. 15) (emphasis omitted). In this regard we note that
“[o]bviousness does not require absolute predictability of success . . . all that
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is required is a reasonable expectation of success,” which, on this record, is
provided by Clark. See In re O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988)).
For the foregoing reasons, we are not persuaded by Clark’s testimony
that “in my scientific opinion, a scientist in the field would not have
considered the term ‘GR modulator’ as used in the Clark application[, of
which declarant is listed as an inventor,] to include GR antagonists for
treating neurodegeneration diseases (Clark Decl. ¶ 11; see id. ¶¶ 5–10 and
evidence cited therein). For the same reasons, we are not persuaded by
Belanoff’s testimony that, as the inventor of the subject matter claimed
herein, “it is my considered opinion that the combination of Clark and
[Carrὶ] does not suggest that a GR modulator might be used to treat ALS”
and “[i]n particular . . . that the combination of Clark and [Carrὶ] does not
suggest that GR modulator (R)-6-(4-tert- Butyl-benzenesulfonyl)-4a-
ethoxymethyl-1-(4-fluoro-phenyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triaza-
cyclopenta[b]naphthalene might be used to treat ALS” (Belanoff Decl.8 ¶¶ 3
and 16; see also id. ¶¶ 4–15 and evidence cited therein). For the foregoing
reasons, we are not persuaded by De Nicola’s testimony that “a scientist in
the field would not consider the cited references when seeking to treat the
symptoms of ALS with a type II GRA” (De Nicola Decl.9 ¶ 15; see also id.
¶¶ 3–14 and evidence cited therein; Appeal Br. 23–26 (citing De Nicola
Decl. ¶¶ 7–9) (Appellant relies on De Nicola’s testimony to support a
contention that “there was no reason to expect that a glucocorticoid
antagonist would be effective at treating ALS”); Appeal Br. 17 (quoting De
Nicola Decl. ¶ 14) (Appellant relies on De Nicola’s testimony to support a

8 Declaration of Joseph K. Belanoff, M.D., signed Dec. 12, 2016.
9 Declaration of Alejandro F. De Nicola, signed June 28, 2019.
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contention that at the time of Appellant’s claimed invention, “there was no
reason to select a GRA to treat any neurodegenerative disease, let alone
ALS”)). For the same reasons, we are not persuaded on Appellant’s reliance
on Fidler10 to support a contention “that a scientist in the field would not
consider treating ALS with a type II GRA” (Appeal Br. 26; see also id. at 27
(citing De Nicola Decl. ¶ 19 (Appellant contends that De Nicola’s testimony
“that a scientist in the field would not consider treating ALS with a type II
GRA [was] based on the Fidler article”); see also Appeal Br. 27–29; Reply
Br. 11–14).
We acknowledge Belanoff’s testimony that Alzheimer’s disease (AD)
and Parkinson’s disease (PD) affect different types of neurons located in
different parts of the brain (see generally Belanoff Decl.11 ¶¶ 5–10). We
note, however, that Clark discloses that its GR modulators can affect a wide
variety of disease states including neurodegeneration, for example
Alzheimer’s disease and Parkinson’s disease (see FF 1). Thus, as Belanoff’s
testimony makes clear, Clark discloses that its GR modulators affect
neurodegenerative disorders implicating different types of neuron and/or
regions of the brain.
For the foregoing reasons, we are not persuaded by Belanoff’s
testimony that because each of ALS, AD, and PD involve different a neuron
types and brain regions Belanoff would not expect Clark’s disclosed
treatment “would be likely to help in treating ALS” (see Belanoff Decl.

10 Fidler et al., Disease progression in a mouse model of amyotrophic lateral
sclerosis: the influence of chronic stress and corticosterone, 25 FASEB J.
4369–4377 (2011).
11 Declaration of Joseph K. Belanoff, M.D., signed Dec. 12, 2016.
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¶¶ 5–10; see also Appeal Br. 16–17 and 21 (Appellant contends, based on
Belanoff’s testimony, that “one of ordinary skill in the art would not have a
reasonable expectation that the same treatment would apply to different
neurodegenerative diseases”)). For the same reasons, we are not persuaded
by Appellant’s reliance on De Nicola’s testimony that “despite being
referred to as a neurodegenerative disease, ALS is a disease with distinct
etiology and pathogenic mechanisms compared to other neurodegenerative
diseases. The cells that are targeted in ALS are motor neurons, whereas the
other neurodegenerative diseases target different cells types in the CNS”
(Appeal Br. 17 (quoting De Nicola Decl. ¶ 14); see also Reply Br. 14 (citing
Belanoff Decl. ¶¶ 5–8) (contending that “different neurodegenerative
diseases affect different cell types”)).
Carrὶ discloses that ALS is a neurodegenerative disorder (FF 6).
Clark discloses the use of Appellant’s elected GRA for the treatment of
neurodegenerative disorders (FF 1–4). Therefore, we are not persuaded by
Appellant’s reliance on Petrov12 to establish that non-GRA compounds were
tested in human ALS clinical trials (Appeal Br. 19–20). For the same
reasons, we are not persuaded by Appellant’s reliance on Cummings13 or
Orayj14 to establish that “no GRAs are approved for treating other
neurodegenerative diseases” (id. at 20; see also id. at 16 (Appellant contends

12 Petrov et al., ALS Clinical Trials Review: 20 Years of Failure. Are we
Any Closer to Registering a New Treatment?, 8 Frontiers in Aging
Neuroscience 1–11 (2017).
13 Cummings et al., Treatment Combinations for Alzheimer’s Disease:
Current and Future Pharmacotherapy Options, 67 Journal of Alzheimer’s
Disease 779–794 (2019).
14 Orayj et al., Patterns and Determinants of Prescribing for Parkingon’s
Disease: A Systematic Literature Review, Parkinson’s Disease 1–40 (2019).
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“that known treatments and clinical trials to treat [Alzheimer’s Disease],
[Parkinson’s Disease] and ALS do not use the same drugs, and instead use
unrelated drugs with totally different mechanisms of action”)).
As discussed above, Clark discloses “a novel class of fused ring
azadecalin compounds[, including Appellant’s elected GRA,] and methods
of using the compounds as glucocorticoid receptor modulators” to treat
neurodegenerative disorders of which ALS “is one of the most common”
(FF 1–4 and 6). Therefore, we are not persuaded by Appellant’s contention
that its claim 1 is “not obvious because one of ordinary skill in the art would
not have been motivated to use a type II GRA to treat ALS based on the
combination of cited references” (Appeal Br. 21). We are also not
persuaded by Appellant’s intimation that it would require undue
experimentation to select Appellant’s elected GRA, which is expressly
exemplified by Clark as a species within its disclosed novel class of fused
ring azadecalin compounds (see id. (Appellant contends that “the skilled
artisan would have to test a very large number of compounds that are
considered GR modulators to arrive at the instant claims”); cf. FF 1–4).
For the foregoing reasons, we are not persuaded by Appellant’s
contentions regarding cortisol (see e.g., Appeal Br. 9, 12, 14, 15, 18, 21, and
24; see also Reply Br. 3–6 and 15). For the same reasons, we are not
persuaded by Appellant’s contentions regarding the GRA disclosed by Sapse
(see e.g., Appeal Br. 24 (citing De Nicola Decl. ¶ 6)).
Weighing the totality of evidence on this record, we find that Clark’s
disclosure of treating neurodegenerative disorders, of which ALS is one of
the most common, with an effective amount of a glucocorticoid receptor
antagonist, including Appellant’s elected GRA outweighs Appellant’s
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contentions that the method of Appellant’s claim 1 “was unexpected in view
of [Appellant’s asserted] substantial skepticism in the art at the time the
instant application was filed” (Appeal Br. 28 (citing De Nicola Decl. and
Hunt Decl.15); see also Reply Br. 9).

Claim 15:
As discussed above, the combination of Clark, Carrὶ, and Sapse makes
obvious the treatment, i.e. amelioration and/or slowing the rate of disease
progression, of a neurodegenerative disorder, such as ALS, in a subject by
administering Appellant’s elected non-steroidal glucocorticoid receptor
specific antagonist (GRA), to a patient in need of such treatment, in an
amount that falls within that required by Appellant’s claimed invention (see
FF 1–6). Therefore, we are not persuaded by Appellant’s contention that
“none of the cited references, alone or in combination, suggest that
[Appellant’s] elected species of GR antagonists can be used to treat ALS”
(Appeal Br. 30).

Claim 25:
As discussed above, because the GRA taught by the combination of
Clark, Carrὶ, and Sapse is the same GRA elected by Appellant, we find no
error in Examiner’s finding that the prior art GRA, inter alia, will
specifically antagonize type II glucocorticoid receptor functions but will not
significantly antagonize type I glucocorticoid receptor (mineralcorticoid
receptor) functions and have a binding affinity for the type II glucocorticoid

15 Declaration of Hazel Hunt, Ph.D., signed July 13, 2016.
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receptor that is at least 100-fold greater than the binding affinity of the GRA
for the type I glucocorticoid receptor (mineralocorticoid receptor) (see, e.g.,
Ans. 8, and 25; see also FF 1–6). Therefore, we are not persuaded by
Appellant’s contention that Sapse’s disclosure of “RU 486, which is a
steroid that binds to the progesterone and glucocorticoid receptors . . . is not
relevant to the instant claims, because it does not specifically antagonize
type II glucocorticoid receptor functions” (Appeal Br. 30).
CONCLUSION
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness. The rejection of claims 1, 15, and 25 under 35
U.S.C. § 103(a) as unpatentable over the combination of Clark, Carrὶ, and
Sapse is affirmed. Claims 17–24 are not separately argued and fall with
claim 1. Claims 26 and 28–33 are not separately argued and fall with claim
25.
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 15,
17–26,
28–33
103(a) Clark, Carrὶ, Sapse 1, 15,
17–26,
28–33

TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED